CN108892743A - For the nanometric photosensitizer of light power antibacterial, preparation method and application - Google Patents
For the nanometric photosensitizer of light power antibacterial, preparation method and application Download PDFInfo
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- CN108892743A CN108892743A CN201810521139.9A CN201810521139A CN108892743A CN 108892743 A CN108892743 A CN 108892743A CN 201810521139 A CN201810521139 A CN 201810521139A CN 108892743 A CN108892743 A CN 108892743A
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- chitosan
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- chlorin
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- 239000003504 photosensitizing agent Substances 0.000 title claims abstract description 89
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 229920001661 Chitosan Polymers 0.000 claims abstract description 121
- 244000000010 microbial pathogen Species 0.000 claims abstract description 12
- 238000001338 self-assembly Methods 0.000 claims abstract description 9
- SURLGNKAQXKNSP-DBLYXWCISA-N chlorin Chemical group C\1=C/2\N/C(=C\C3=N/C(=C\C=4NC(/C=C\5/C=CC/1=N/5)=CC=4)/C=C3)/CC\2 SURLGNKAQXKNSP-DBLYXWCISA-N 0.000 claims description 65
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 60
- 239000012264 purified product Substances 0.000 claims description 18
- 239000012043 crude product Substances 0.000 claims description 17
- 239000003153 chemical reaction reagent Substances 0.000 claims description 15
- 239000000047 product Substances 0.000 claims description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 8
- 230000008878 coupling Effects 0.000 claims description 7
- 238000010168 coupling process Methods 0.000 claims description 7
- 238000005859 coupling reaction Methods 0.000 claims description 7
- 229920005654 Sephadex Polymers 0.000 claims description 6
- 239000012507 Sephadex™ Substances 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 2
- 230000006196 deacetylation Effects 0.000 claims description 2
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- 230000035479 physiological effects, processes and functions Effects 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000011260 aqueous acid Substances 0.000 claims 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims 1
- 239000000052 vinegar Substances 0.000 claims 1
- 235000021419 vinegar Nutrition 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract description 15
- 229920000642 polymer Polymers 0.000 abstract description 4
- 238000012412 chemical coupling Methods 0.000 abstract description 3
- 230000009881 electrostatic interaction Effects 0.000 abstract description 3
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- 239000000243 solution Substances 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- -1 hydroxyl free radical Chemical class 0.000 description 21
- 241000588724 Escherichia coli Species 0.000 description 11
- 241000191967 Staphylococcus aureus Species 0.000 description 10
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- 230000004913 activation Effects 0.000 description 8
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- 238000003756 stirring Methods 0.000 description 7
- PLPFBVXTEJUIIT-UHFFFAOYSA-N 1,2-dimethylanthracene Chemical compound C1=CC=CC2=CC3=C(C)C(C)=CC=C3C=C21 PLPFBVXTEJUIIT-UHFFFAOYSA-N 0.000 description 6
- 244000063299 Bacillus subtilis Species 0.000 description 6
- 235000014469 Bacillus subtilis Nutrition 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- 241000589291 Acinetobacter Species 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 5
- 206010041925 Staphylococcal infections Diseases 0.000 description 5
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- 238000010521 absorption reaction Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
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- 230000003287 optical effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 2
- JTGMTYWYUZDRBK-UHFFFAOYSA-N 9,10-dimethylanthracene Chemical compound C1=CC=C2C(C)=C(C=CC=C3)C3=C(C)C2=C1 JTGMTYWYUZDRBK-UHFFFAOYSA-N 0.000 description 2
- 239000002028 Biomass Substances 0.000 description 2
- 229920001503 Glucan Polymers 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 239000012317 TBTU Substances 0.000 description 2
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 229920006317 cationic polymer Polymers 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
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- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- RKCAIXNGYQCCAL-UHFFFAOYSA-N porphin Chemical compound N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 RKCAIXNGYQCCAL-UHFFFAOYSA-N 0.000 description 2
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LXJOYRVJPWDJBZ-UHFFFAOYSA-N (2-acetamido-3-hydroxyphenyl)arsonic acid Chemical compound OC=1C(=C(C=CC1)[As](O)(O)=O)NC(C)=O LXJOYRVJPWDJBZ-UHFFFAOYSA-N 0.000 description 1
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- GLAZMGQANOHRCR-UHFFFAOYSA-N 5-(chloromethyl)-1h-1,2,4-triazole Chemical compound ClCC1=NC=NN1 GLAZMGQANOHRCR-UHFFFAOYSA-N 0.000 description 1
- PZKFSRWSQOQYNR-UHFFFAOYSA-N 5-methyl-1h-1,2,4-triazole Chemical compound CC1=NC=NN1 PZKFSRWSQOQYNR-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- IPCRBOOJBPETMF-UHFFFAOYSA-N N-acetylthiourea Chemical compound CC(=O)NC(N)=S IPCRBOOJBPETMF-UHFFFAOYSA-N 0.000 description 1
- WZHKCFDUDKJGBA-UHFFFAOYSA-N N1CCNCC1.S1C=CC=C1 Chemical class N1CCNCC1.S1C=CC=C1 WZHKCFDUDKJGBA-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
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- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical compound NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940042396 direct acting antivirals thiosemicarbazones Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- HOCOIDRZLNGZMV-UHFFFAOYSA-N ethoxy(oxido)phosphanium Chemical compound CCO[PH2]=O HOCOIDRZLNGZMV-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000004031 fumaroyl group Chemical group C(\C=C\C(=O)*)(=O)* 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
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- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
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- 239000002547 new drug Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
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- 239000011664 nicotinic acid Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
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- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- NNOBHPBYUHDMQF-UHFFFAOYSA-N propylphosphine Chemical compound CCCP NNOBHPBYUHDMQF-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
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- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 231100000489 sensitizer Toxicity 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003583 thiosemicarbazides Chemical group 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylene diamine Substances C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Materials Engineering (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of nanometric photosensitizer for light power antibacterial, preparation method and application.The present invention reacts photosensitizer with chitosan or chitosan derivatives by chemical Coupling, obtains the chitosan or derivatives thereof of photosensitizer grafting, this amphiphilic polymer can be self-assembly of nanometric photosensitizer.This nanometric photosensitizer improves the hydrophobicity of prototype photosensitizer, improves its stability and biocompatibility.Furthermore, the chitosan or derivatives thereof of photosensitizer grafting forms positively charged nanometric photosensitizer in physiological solution, it can preferably be absorbed by pathogenic microorganism by electrostatic interaction, under the action of visible light/near infrared light, singlet oxygen is converted by the oxygen molecule in environment, can be used for light power antibacterial.
Description
Technical field
The present invention relates to the technical fields such as optical application, nanosystems, pathogenic microorganism prevention, and in particular to a kind of light is dynamic
Resist the nanometric photosensitizer of bacterium, preparation method and application strenuously.
Background technique
Since twentieth century, the appearance of multi-drug resistant bacteria is caused along with abuse of antibiotics, has seriously threatened public affairs
Many health research and develop new drug and new treatment means substitute antibiotics treatment, have become grinding for every country research work
Study carefully hot spot.Wherein optical dynamic therapy antibacterial has been subjected to widely paying close attention to as a kind of new treatment means.
Light power antibacterial is mainly made of photosensitizer and suitable light source.Under the irradiation of suitable sources, sensitiser absorption
The light of short wavelength, by ground state (S0) transitted to singlet (S1) it is changed into excited triplet state (T again1), then by excited triplet state
(T1) react with the oxygen molecule in surrounding medium, generate hydroxyl free radical (OH) or singlet oxygen (1O2) isoreactivity object
Matter further acts on thallus, oxidation reaction can occur with the large biological molecule (lipid, protein, nucleic acid) of thallus, make thallus
Damage, apoptosis.Photosensitizer (photosensitizer, hereinafter referred to as PS) is existing as the critical mediator during light power antibacterial
It include thiophene piperazine class studying more photosensitizer, porphyrin and chlorin e 6 class etc., most of photosensitizers (PS) are in water
Solubility it is extremely low, and have the shortcomings that unstable, easy aggregation in aqueous solution, seriously hinder it in light power antibacterial
It is widely applied.
Summary of the invention
The purpose of the present invention is to provide a kind of preparation methods of nanometric photosensitizer for light power antibacterial.
To realize the above-mentioned technical purpose, the present invention adopts the following technical scheme that：
It by photosensitizer, coupling reagent co-dissolve in organic solvent, is activated under the conditions of being protected from light, chitosan is added later
Under the conditions of being protected from light in the aqueous acetic acid of aqueous acetic acid or chitosan derivatives reaction produce photosensitizer grafting chitosan or
The crude product of its derivative, finally purifies crude product and obtains purified product, and purified product is self-assembly of in physiological solution
The nanometric photosensitizer.
Chitosan and its derivative (CS) is one kind by 2- acetylaminohydroxyphenylarsonic acid 2- deoxidation-D- pyrans glucan and 2- amino -2-
Based on deoxidation-D- pyrans glucan, with polysaccharide polymer made of β-Isosorbide-5-Nitrae-glucosides key connection, there is good bio-compatible
Property and the characteristics such as safety and low toxicity, had in medicine, chemical industry, food and nutrition, agricultural with fields such as environmental protections and widely answered
With.As natural cationic polymer, chitosan or chitosan derivatives can be with microbial cell surfaces with negative electrical charge
Large biological molecule combines, and improves pathogenic microorganism to the uptake ratio of nanometric photosensitizer, improves the effect of optical dynamic therapy.
The photosensitizer of activation (PS) is reacted with chitosan or chitosan derivatives by chemical Coupling in the present invention, is obtained
The chitosan or chitosan derivatives of photosensitizer grafting, this amphiphilic polymer can be self-assembly of nanometric photosensitizer.It is this
Nanometric photosensitizer improves the hydrophobicity of photosensitizer (PS), improves the stability and biocompatibility of photosensitizer (PS).In addition,
The chitosan or derivatives thereof of photosensitizer grafting forms positively charged nanometric photosensitizer in physiological solution, passes through electrostatic interaction
It can preferably be absorbed by pathogenic microorganisms, further under the action of visible light/near infrared light, by the oxygen molecule in environment
Be converted into strong cytotoxicity singlet oxygen (1O2), it can be used as the excellent photosensitizer of light power antibacterial, be applied to a variety of diseases
The killing and inhibition of pathogenic microorganism.
Further, the coupling reagent is selected from following any：
The mix reagent of n-hydroxysuccinimide (NHS) and N, N '-dicyclohexylcarbodiimide (DCC)；It is preferred that rub
You are than 1: 1 mixing；
Or triethylamine (Et3N) with O- benzotriazole-tetramethylurea hexafluorophosphate (HBTU) mix reagent；It is preferred that with
Molar ratio 1: 1 mixes；
Or N, N- diisopropylethylamine (DIPEA) and O- benzotriazole-N, N, N', N'- tetramethylurea tetrafluoroborate
(TBTU) mix reagent；It is preferred that with the mixing of molar ratio 2: 1；
Or N, N- diisopropylethylamine (DIPEA), I-hydroxybenzotriazole (HOBt) and 1- ethyl-(3- dimethylamino
Propyl) carbodiimide hydrochloride (EDCHCl) mix reagent；It is preferred that with the mixing of molar ratio 2: 1: 1；
Further, the organic solvent selects dimethyl sulfoxide or dimethylformamide.
Further, the molar ratio of the photosensitizer and coupling reagent is 1: 4-1: 16.
Further, the aqueous acetic acid or chitosan derivatives for the chitosan that addition mass fraction is 0.5%-4%
Crude product is produced in reaction under the conditions of being protected from light in aqueous acetic acid.
Further, the molecular weight ranges of the chitosan or chitosan derivatives are 5 × 103-3×105Da, it is deacetylated
Degree range is 55%-95%.
Further, the photosensitizer is chlorin e 6 (Ce6)；
Further, crude product is washed by sephadex column with the aqueous acetic acid that mass fraction is 0.5%-3%
It is de-, purified product is obtained, purified product is transferred in bag filter dialyses by medium of physiological solution to get to receiving later
Rice photosensitizer.
Further, in the nanometric photosensitizer, photosensitizer is grafted to the grafting rate of chitosan or chitosan derivatives
Range is 1%-10%.
Another object of the present invention is to provide the nanometric photosensitizers of above method preparation.
Another object of the present invention is to provide the nanometric photosensitizer to inhibit the application in pathogenic microorganism.The present invention
Product chitosan graft photosensitizer or chitosan derivatives grafting photosensitizer (PS-CS) compound be positively charged nanometer light
It quick dose, can preferably be absorbed by pathogenic microorganisms by electrostatic interaction, further in the effect of visible light/near infrared light
Under, by the oxygen molecule in environment be converted into strong cytotoxicity singlet oxygen (1O2), it can be used as the excellent photosensitive of light power antibacterial
Agent, killing and inhibition applied to multiple pathogenic microorganisms.
Chitosan derivatives of the present invention are the compound that substitution reaction and modification occur for a kind of hydroxy functional group, are answered
When with following structural formula：
For example, it may be benzoylchitosan ester, para hydroxybenzene aminobenzoyl chitosan ester, fumaroyl chitosan, sorb acyl shell
Glycan, N- (2- Hydroxyproyl Trimethyl) chitosan, N, O- Carboxymethyl chitosan, O- Carboxymethyl chitosan, O- carboxyethylation
Chitosan, diethylmethyl chitosan, chitosan acetyl thiourea, chitosan chloracetyl thiocarbamide, 3- methyl-1,2,4- triazole
Chitosan, 3- chloromethyl -1,2,4- triazole chitosan, chitosan benzoic acid alkynes propyl ester 1,2,3- triazole, chitosan niacin alkynes third
Ester 1,2,3- triazole, chitosan alkyl dithiocarbamate, chitosan aminodithioformic acid triethylene diamine salt, shell are poly-
Sugared thiosemicarbazides, chitosan substituted-phenyl thiosemicarbazones, chitosan dithiocar-bamate, chitosan alpha-amido normal-butyl
Phosphinic acid ethyl ester, chitosan alpha-amido n-propyl phosphine acetoacetic ester, chitosan alpha-amino-benzene oxygen pyrimidine methyl-phosphonate, chitosan alpha-ammonia
Phenoxyl pyrimidine phosphinic acid ethyl ester, chitosan alpha-amino furan base methyl-phosphonate, chitosan alpha-amino furan base phosphinic acid ethyl ester, shell
Glycan Zn complex, chitosan nickel complex, chitosan mantoquita, chitosan zinc salt etc..
The present invention passes through the photosensitizer (PS) that will be activated and chitosan or nanometer light is made in chitosan derivatives chemical Coupling
The hydrophobicity of quick dose of PS-CS, photosensitizer (PS) have obtained apparent improvement, improve the stabilization of photosensitizer (PS) in aqueous solution
Property and biocompatibility；In addition, nanometric photosensitizer PS-CS is a kind of cationic polymer, be conducive to by multiple pathogenic microorganisms
It is absorbed.In the case where wavelength is the laser irradiation of 660nm, nanometric photosensitizer PS-CS can be converted the oxygen molecule in ambient enviroment
For singlet oxygen, it can be applied to Escherichia coli (hereinafter referred to as E.coli), staphylococcus aureus (hereinafter referred to as SA), resistance to
Methicillin staphylococcus aureus (hereinafter referred to as MRSA), bacillus subtilis (hereinafter referred to as BS), Bao Man not lever
The killing of the multiple pathogenic microorganisms such as bacterium (hereinafter referred to as AB) and process of inhibition.
Detailed description of the invention
Fig. 1 is the flow chart of preparation method of the present invention；
Fig. 2 be the UV-visible absorption spectrum of PS-CS nanometric photosensitizer obtained in the embodiment of the present invention 1 (wherein
PS-CS is Ce6-Chitosan)；
Fig. 3 be the dynamic light scattering grain size distribution of PS-CS nanometric photosensitizer obtained in the embodiment of the present invention 1 (wherein
PS-CS is Ce6-Chitosan)；
Fig. 4 is that (wherein PS-CS is Ce6- for the infrared spectrogram of PS-CS nanometric photosensitizer obtained in the embodiment of the present invention 1
Chitosan)；
Fig. 5 is that (wherein PS-CS is for the singlet oxygen measurement chart of PS-CS nanometric photosensitizer obtained in the embodiment of the present invention 1
Ce6-Chitosan)；
Fig. 6 be in the embodiment of the present invention 1 PS-CS nanometric photosensitizer obtained to the fungistatic effect figures of Escherichia coli (wherein
PS-CS is Ce6-Chitosan)；
Fig. 7 is PS-CS nanometric photosensitizer obtained in the embodiment of the present invention 1 to the fungistatic effect figure of staphylococcus aureus
(wherein PS-CS is Ce6-Chitosan)；
Fig. 8 is PS-CS nanometric photosensitizer obtained in the embodiment of the present invention 1 to methicillin-resistant staphylococcus aureus
Fungistatic effect figure (wherein PS-CS is Ce6-Chitosan)；
Fig. 9 is PS-CS nanometric photosensitizer obtained in the embodiment of the present invention 1 to the fungistatic effect figure of bacillus subtilis
(wherein PS-CS is Ce6-Chitosan)；
Figure 10 is PS-CS nanometric photosensitizer obtained in the embodiment of the present invention 1 to the fungistatic effect figure of Acinetobacter bauamnnii
(wherein PS-CS is Ce6-Chitosan).
Specific embodiment
The present invention is further detailed with embodiment with reference to the accompanying drawing.
Attached drawing 1 is the flow chart of preparation method of the present invention.The present invention is by by photosensitizer (PS), coupling reagent co-dissolve
In organic solvent, it is protected from light photosensitizer (PS) solution that activation is made in temperature control stirring；Photosensitizer (PS) solution of activation is added to
Temperature control stirring is carried out in the aqueous acetic acid of chitosan or the aqueous acetic acid of chitosan derivatives, obtains PS-CS crude product；
PS-CS crude product affords PS-CS purified product by sephadex column, and using aqueous acetic acid；PS-CS is purified
Product is dialysed by medium of physiological solution, Simultaneous purification product be self-assembly of in physiological solution PS-CS nanometers it is photosensitive
Agent.
Photosensitizer selects chlorin e 6 (Ce6) in embodiment.The molecular weight ranges of chitosan or chitosan derivatives are 5
×103-3×105Da, deacetylation range are 55%-95%.
Embodiment 1
S1：N, N '-dicyclohexylcarbodiimide (DCC) 6.9mg, n-hydroxysuccinimide (NHS) 4.0mg are weighed respectively
It is dissolved in 10mL dimethyl sulfoxide (DMSO) with after chlorin e 6 (Ce6) 10mg mixing, is obtained after lower stirring 0.5h is protected from light at 25 DEG C
Chlorin e 6 solution after to activation；
S2：After chlorin e 6 solution after activation is removed insoluble type by-product with membrane filtration, it is slowly added dropwise to matter
It measures in the chitosan aqueous acetic acid (100mL) that score is 0.5%, is protected from light under the conditions of 25 DEG C and is stirred to react 12h, obtain dihydro
Porphines e6 grafted chitosan (Ce6-Chitosan) crude product；
S3：Chlorin e 6 grafted chitosan (Ce6-Chitosan) crude product in solution is taken to be added dropwise on sephadex column
Side is eluted with the aqueous acetic acid that mass fraction is 0.5% after entering gel inside, it is poly- to obtain chlorin e 6 graft shell
Sugared (Ce6-Chitosan) purified product.
S4：Chlorin e 6 grafted chitosan (Ce6-Chitosan) purified product is transferred in bag filter, molten with physiology
Liquid is dialyzed overnight for medium, and Simultaneous purification product is self-assembly of chlorin e 6 grafted chitosan (Ce6- in physiological solution
Chitosan) nanometric photosensitizer；Wherein the molecule interception of bag filter is 12000, in product chlorin e 6 grafted chitosan
The grafting rate range that chlorin e 6 is grafted to chitosan is 1%-10%.
Embodiment 2
S1：Triethylamine (Et is weighed respectively3N) 8.4mg, O- benzotriazole-tetramethylurea hexafluorophosphoric acid ester (HBTU)
It is dissolved in 10mL dimethylformamide (DMF) after 31.6mg and chlorin e 6 (Ce6) 10mg mixing, is protected from light lower stirring at 20 DEG C
Chlorin e 6 solution after being activated after 12h；
S2：After chlorin e 6 solution after activation is removed insoluble type by-product with membrane filtration, it is slowly added dropwise to matter
It measures in N- (2- Hydroxyproyl Trimethyl) the chitosan aqueous acetic acid (100mL) that score is 3.2%, is protected from light stirs at 20 °C
It mixes reaction for 24 hours, obtains chlorin e 6 graft N-(2- Hydroxyproyl Trimethyl) chitosan crude product；
S3：Chlorin e 6 graft N-(2- Hydroxyproyl Trimethyl) chitosan crude product in solution is taken to be added dropwise to sephadex
Above column, after entering gel inside, it is purified by flash with the aqueous acetic acid that mass fraction is 1%, obtains chlorin e 6 and connect
Branch N- (2- Hydroxyproyl Trimethyl) chitosan purified product；
S4：Chlorin e 6 graft N-(2- Hydroxyproyl Trimethyl) chitosan purified product is transferred in bag filter, with
Physiological solution is dialyzed overnight for medium, and Simultaneous purification product is self-assembly of chlorin e 6 graft N-(2- in physiological solution
Hydroxyproyl Trimethyl) chitosan nano photosensitizer；Wherein the molecule interception of bag filter is 12000, and product chlorin e 6 connects
It is poly- to be grafted to N- (2- Hydroxyproyl Trimethyl) shell for chlorin e 6 in branch N- (2- Hydroxyproyl Trimethyl) chitosan nano photosensitizer
The grafting rate range of sugar is 1%-10%.
Embodiment 3
S1：N,N-diisopropylethylamine (DIPEA) 17.3mg, O- benzotriazole-N, N, N', N'- tetramethyl is weighed respectively
10mL dimethylformamide is dissolved in after base urea tetrafluoro boric acid ester (TBTU) 21.4mg and chlorin e 6 (Ce6) 5mg mixing
(DMF), be protected from light at 30 DEG C it is lower stirring 6h after activated after chlorin e 6 solution；
S2：After chlorin e 6 solution after activation is removed insoluble type by-product with membrane filtration, it is slowly added dropwise to matter
It measures in chitosan alpha-amino-benzene oxygen pyrimidine phosphinic acid ethyl ester aqueous acetic acid (50mL) that score is 3.2%, under the conditions of 30 DEG C
It is protected from light 48h, obtains chlorin e 6 grafted chitosan alpha-amido phenoxy pyrimidine phosphinic acid ethyl ester crude product；
S3：Chlorin e 6 grafted chitosan alpha-amido phenoxy pyrimidine phosphinic acid ethyl ester crude product in solution is taken to be added dropwise to Portugal poly-
Above sugared gel column, after entering gel inside, it is purified by flash with the aqueous acetic acid that mass fraction is 2%, obtains dihydro porphin
Pheno e6 grafted chitosan alpha-amido phenoxy pyrimidine phosphinic acid ethyl ester purified product；
S4：Chlorin e 6 grafted chitosan alpha-amido phenoxy pyrimidine phosphinic acid ethyl ester purified product is transferred to bag filter
It is interior, it is dialyzed overnight by medium of physiological solution, Simultaneous purification product is self-assembly of chlorin e 6 grafting in physiological solution
Chitosan alpha-amino-benzene oxygen pyrimidine phosphinic acid ethyl ester nanometric photosensitizer；Wherein the molecule interception of bag filter is 12000, product two
Chlorin e 6 is grafted to chitosan in hydrogen porphines e6 grafted chitosan alpha-amido phenoxy pyrimidine phosphinic acid ethyl ester nanometric photosensitizer
The grafting rate range of alpha-amido phenoxy pyrimidine phosphinic acid ethyl ester is 1%-10%.
Embodiment 4
S1：N,N-diisopropylethylamine (DIPEA) 17.2mg, I-hydroxybenzotriazole (HOBt) 9.1mg, 1- are weighed respectively
Ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride (EDCHCl) 12.8mg and chlorin e 6 (Ce6) 10mg are mixed
10mL dimethylformamide (DMF) is dissolved in after mixing, be protected from light at 40 DEG C it is lower stirring 6h after activated after chlorin e 6 it is molten
Liquid；
S2：After chlorin e 6 solution after activation is removed insoluble type by-product with membrane filtration, it is slowly added dropwise to matter
The diethylmethyl chitosan aqueous acetic acid (80mL) that score is 4% is measured, 48h is protected from light under the conditions of 40 DEG C, obtains two
Hydrogen porphines e6 is grafted diethylmethyl chitosan crude product；
S3：Chlorin e 6 grafting diethylmethyl chitosan crude product in solution is taken to be added dropwise to above sephadex column,
It after entering gel inside, is purified by flash with the aqueous acetic acid that mass fraction is 3%, obtains chlorin e 6 grafting diethyl
Methyl chitosan purified product；
S4：Chlorin e 6 grafting diethylmethyl chitosan purified product is transferred in bag filter, with physiological solution
It is dialyzed overnight for medium, it is poly- that Simultaneous purification product is self-assembly of chlorin e 6 grafting diethylmethyl shell in physiological solution
Sugared photosensitizer, wherein the molecule interception of bag filter is 12000, and it is photosensitive that product chlorin e 6 is grafted diethylmethyl chitosan
The grafting rate range that chlorin e 6 is grafted to diethylmethyl chitosan in agent is 1%-10%.
Embodiment 5
Embodiment 5 illustrates product chlorin e 6 grafted chitosan (Ce6-Chitosan) property of embodiment 1.
Fig. 2 is chlorin e 6 (Ce6), chlorin e 6 grafted chitosan (Ce6-Chitosan) and chitosan
(Chitosan) UV-visible absorption spectrum of the aqueous solution in 300-800nm；As can be seen from the figure chitosan does not have substantially
There are absorption, chlorin e 6 and chlorin e 6 grafted chitosan to have an apparent absorption peak in 400nm and 650nm, shows
Success chlorin e 6 grafted chitosan；
Fig. 3 is the dynamic light scattering grain size distribution of chlorin e 6 grafted chitosan (Ce6-Chitosan) aqueous solution；
As can be seen from the figure the average aquation partial size of chlorin e 6 grafted chitosan (Ce6-Chitosan) is 346 ± 15.9nm,
Show that chlorin e 6 grafted chitosan is nanometer polymer；
Fig. 4 is chlorin e 6 grafted chitosan (Ce6-Chitosan) aqueous solution in 4000-500cm-1Infrared spectroscopy
Figure；1078cm known in figure-1It is the stretching vibration absworption peak of chitosan C-O-C；1707cm-1、3419cm-1It is dihydro porphin respectively
The stretching vibration absworption peak of the C=O and OH of pheno e6 show chlorin e 6 success grafted chitosan；
Fig. 5 is the singlet oxygen measurement chart of chlorin e 6 grafted chitosan (Ce6-Chitosan) solution；Using 9,10-
Dimethylanthracene (DMA) detects singlet oxygen, and 9,10- dimethylanthracene is dissolved in n,N-Dimethylformamide solution (DMF), is added
Chlorin e 6 grafted chitosan (Ce6-Chitosan) solution of 0.5-1mL, in the laser prolonged exposure that wavelength is 660nm
After 10-30min, solution fluorescence intensity is detected under 374nm exciting light, DMA launches strong fluorescence in 475nm in figure；DMA
With chlorin e 6 grafted chitosan mixed solution after 660nm laser irradiation, chlorin e 6 grafted chitosan generates single line
After state oxygen and DMA (singlet oxygen capturing agent) combine, so that the structure of DMA changes, fluorescent quenching；Swashing without 660nm
The DMA and chlorin e 6 grafted chitosan mixed solution of light irradiation launch strong fluorescence in 475nm, illustrate in 660nm
Laser irradiation under chlorin e 6 grafted chitosan (Ce6-Chitosan) singlet oxygen can be generated.
Embodiment 6
This example demonstrates that nanometric photosensitizer of the invention is inhibiting the application in pathogenic microorganism.
By taking the product chlorin e 6 grafted chitosan nanometric photosensitizer (Ce6-Chitosan) of embodiment 1 as an example, specifically
Experimental procedure is as follows：
S1：By Escherichia coli (hereinafter referred to as E.coli), staphylococcus aureus (hereinafter referred to as SA), resistance to methoxy west
Woods staphylococcus aureus (hereinafter referred to as MRSA), bacillus subtilis (hereinafter referred to as BS), Acinetobacter bauamnnii are (following
Referred to as AB) it is inoculated in fluid nutrient medium respectively, 37 DEG C are placed in shaking table, and 200rpm cultivates 12h；
S2：The bacterium solution of overnight incubation is taken to be washed respectively with phosphate buffer (pH 7.4) and be diluted to suitable concentration
(absorbance 0.5), then the water of addition phosphate buffer (pH 7.4) or chlorin e 6 grafted chitosan into bacterium solution
Solution (volume ratio 9：1), wherein phosphate buffer is control group, and chlorin e 6 grafted chitosan is experimental group；
S3：By thallus mixed liquor after 660nm laser irradiation 15min, certain volume thallus mixed liquor is taken after illumination
It is inoculated in fluid nutrient medium, is placed in shaking table 37 DEG C, 200rpm culture samples the extinction of simultaneously test sample in different time points
Degree examines or check the fungistatic effect of chlorin e 6 grafted chitosan nanometric photosensitizer；
Fig. 6-10 is phosphate buffer (control group) and (experiment of chlorin e 6 grafted chitosan nanometric photosensitizer respectively
Group) to Escherichia coli (hereinafter referred to as E.coli), staphylococcus aureus (hereinafter referred to as SA), methicillin-resistant staphylococcus
Staphylococcus (hereinafter referred to as MRSA), bacillus subtilis (hereinafter referred to as BS), Acinetobacter bauamnnii are (hereinafter referred to as
AB fungistatic effect figure)；As can be seen from the figure Escherichia coli (hereinafter referred to as E.coli), staphylococcus aureus are (following
Referred to as SA), methicillin-resistant staphylococcus aureus (hereinafter referred to as MRSA), bacillus subtilis (hereinafter referred to as
BS), Acinetobacter bauamnnii (hereinafter referred to as AB) cultivates 2h after treatment, and control group and experimental group do not have significant difference, with
The extension of incubation time, exponential increase is presented in the biomass of control group and the biomass of experimental group does not change, and shows to test
Group flora is suppressed completely, and chlorin e 6 grafted chitosan is to Escherichia coli (hereinafter referred to as E.coli), golden yellow grape
Coccus (hereinafter referred to as SA), methicillin-resistant staphylococcus aureus (hereinafter referred to as MRSA), bacillus subtilis are (following
Referred to as BS), Acinetobacter bauamnnii (hereinafter referred to as AB) all have good fungistatic effect.
Antibacterial test is carried out to the chlorin e 6 grafted chitosan derivates nanometer photosensitizer of embodiment 2-4, effect is such as
Shown in following table：
The fungistatic effect table of 1 chlorin e 6 grafted chitosan derivates nanometer photosensitizer of table
Remarks："-" indicates that target flora is suppressed completely
The present invention is described by embodiment, and those skilled in the art know, is not departing from spirit of the invention
In the case where range, various changes or equivalence replacement can be carried out to these features and embodiment.In addition, in finger of the invention
It leads down, can modify to these features and embodiment to adapt to particular situation and material without departing from spirit of the invention
And range.Therefore, the present invention is not limited to the particular embodiment disclosed, in fallen with claims hereof
Embodiment shall fall within the protection scope of the present invention.
Claims (10)
1. a kind of preparation method of the nanometric photosensitizer for light power antibacterial, which is characterized in that photosensitizer, coupling reagent is total
It with being dissolved in organic solvent, is activated under the conditions of being protected from light, the aqueous acetic acid or chitosan derivatives of chitosan is later added
In aqueous acetic acid, the crude product of chitosan of photosensitizer grafting or derivatives thereof is produced in reaction under the conditions of being protected from light, finally to thick
Purification of products obtains purified product, and purified product is self-assembly of the nanometric photosensitizer in physiological solution.
2. the method according to claim 1, wherein the coupling reagent is selected from following any one or several groups
It closes：
N-hydroxysuccinimide and N, the mix reagent of N '-dicyclohexylcarbodiimide；
Or triethylamine and O- benzotriazole-tetramethylurea hexafluorophosphate mix reagent；
Or the mix reagent of N, N- diisopropylethylamine and O- benzotriazole-N, N, N', N'- tetramethylurea tetrafluoroborate；
Or N, N- diisopropylethylamine, I-hydroxybenzotriazole and 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride
The mix reagent of salt.
3. the method according to claim 1, wherein the organic solvent selects dimethyl sulfoxide or dimethyl methyl
Amide.
4. the method according to claim 1, wherein the molar ratio of the photosensitizer and coupling reagent is 1: 4-1:
16。
5. the method according to claim 1, wherein the vinegar for the chitosan that mass fraction is 0.5% -4% is added
Crude product is produced in reaction under the conditions of being protected from light in the aqueous acetic acid of aqueous acid or chitosan derivatives.
6. the method according to claim 1, wherein the molecular weight model of the chitosan or chitosan derivatives
Enclose is 5 × 103 - 3×105 Da, deacetylation range are 55% -95%.
7. method according to claim 1 or 6, which is characterized in that the photosensitizer is chlorin e 6 (Ce6).
8. the method according to claim 1, wherein crude product is passed through sephadex column mass fraction
It is eluted for 0.5% -3% aqueous acetic acid, obtains purified product, purified product is transferred in bag filter later molten with physiology
Liquid is that medium is dialysed to get nanometric photosensitizer is arrived.
9. the nanometric photosensitizer of any one of claim 1 ~ 8 the method preparation.
10. nanometric photosensitizer described in claim 9 is inhibiting the application in pathogenic microorganism.
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